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J F Colombel

Publications and source records attributed to J F Colombel.

At least 109 records · Page 6Linked to original sources
PubMed1997

Significance of interleukin-1beta and interleukin-1 receptor antagonist genetic polymorphism in inflammatory bowel diseases.

OBJECTIVE: Genetic susceptibility to inflammatory bowel disease is well recognized. There is also increasing evidence for the activation of the mucosal immune system and the production of inflammatory cytokines, i.e., interleukin (IL)-1ra and IL-1beta in the inflammatory bowel disease. The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease. METHODS: Two hundred twenty-eight inflammatory bowel disease patients (87 UC and 141 CD) were included in this study and compared with 113 unrelated controls. The IL-1beta and IL-1ra gene polymorphism was studied after specific amplification of variable regions by PCR. A penta-allelic polymorphism, corresponding to a VNTR region located in intron 2 of the IL-1ra gene, was analyzed, whereas bi-allelic RFLPs displayed by two restriction enzymes (TaqI and AvaI) at position -511 of the IL-1beta gene were analyzed. RESULTS: There was no significant difference of genotype distribution between controls and CD or UC patients. However, surgically treated UC patients were characterized by a higher frequency of genotype IL-1ra 1-2 (39 vs 16%, pc < 0.01) compared with nonoperated UC patients. Moreover, nonoperated UC patients displayed a lower frequency of IL-1ra allele 2 than surgically treated UC patients (14 vs 34%, pc < 0.002) or controls (14 vs 30%, pc < 0.005). Furthermore, simultaneous analysis of the IL-1beta and IL-1ra genes that are located in the same region of chromosome 2 revealed that CD patients carrying the IL-1beta allele 2 were more often noncarriers of IL-1ra allele 2 (p < 0.005). Moreover, UC and CD patients were, characterized by a lower frequency of the association of IL-1ra allele 2 and IL-1beta allele 2 compared with controls (8.3 vs 20.3% and 10.6 vs 20.3%, p < 0.03). CONCLUSIONS: IL-1ra and IL-1beta gene polymorphism analysis from a clinical standpoint might help in defining UC prognosis. However, functional studies at both the circulating and mucosal level with stratification on allele associations, especially IL-1ra allele 2-IL-1beta allele 2 subgroups must be realized before therapeutic implications.

Adult↗
PubMed1997

Impact of surgery on quality of life in Crohn's disease.

OBJECTIVE: Health-related quality of life (HRQOL) status is an important component in assessing the impact of disease and its treatments in patients with chronic disorders. We recently validated a HRQOL questionnaire in French patients with inflammatory bowel disease. The aim of this study was to evaluate prospectively the impact of surgery on HRQOL in patients operated on for Crohn's disease (CD). METHODS: Twenty-six patients (14 women, 12 men; median age 28.5 yr) undergoing an elective ileocolonic resection for CD were studied. The HRQOL questionnaire comprised a general questionnaire of 36 items (Medical Outcomes Study-Short Form 36), to which was added a sleep module, and a specific questionnaire of 28 items (Rating Form of Inflammatory Bowel Disease Patient Concerns), to which were added three independent items because of their pertinence in the French population. HRQOL was assessed immediately preoperatively and 3 months postoperatively. RESULTS: HRQOL was improved postoperatively compared with the immediate preoperative status in almost all scales. Patient concerns and worries decreased after surgery. However, ranking was unchanged for the five most intense concerns: having an ostomy bag, having surgery, energy level, uncertainty of the disease, and pain or suffering. CONCLUSIONS: HRQOL is greatly improved after surgery for CD, and this reassuring message might be delivered to our patients. In addition, the questionnaire showed the ability to detect clinical changes over time. This attests to its potential use in research.

Adult↗
PubMed1997

[Amyloidosis AL of the breast in an ileal carcinoid tumor].

An ileal tumor was detected in a patient with monoclonal plasmocytosis of the bone marrow (IgA Kappa). The pathological examination showed a carcinoid tumor with amyloid stroma. Immunotyping of the amyloidosis showed that it was stained with the antibody directed against light chain kappa, though the amyloidosis was located within a carcinoid tumor.

Amyloidosis↗
PubMed1997

[Pseudotumor nodular lymphoid hyperplasia of the ileum].

We report a case of pseudotumoral nodular lymphoid hyperplasia of the ileum in an immunocompetent 62-year-old woman. Ileoscopy showed multiple voluminous, soft, pliable, polypoid ileal lesions. Perendoscopic biopsies revealed a florid inflammation of the mucosa, characterised by numerous enlarged follicles with well-developed reactive germinal centres separated by a mixed infiltrate of lymphocytes, plasma cells and eosinophils. Immunohistochemistry showed a polytypic staining for kappa and lambda light-chains in the follicles and between and confirmed the reactive nature of the infiltrate. CT scan of the abdomen disclosed large periileal lymph nodes and a right ileocolectomy was performed. Twelve cases of pseudotumoral nodular lymphoid hyperplasia of the ileum have been reported in the literature in patients older than 25. In all cases, the diagnosis was performed after laparotomy. As shown in our case report, the diagnosis is possible on multiple perendoscopic biopsies.

Castleman Disease↗
PubMed1996

Mapping of a susceptibility locus for Crohn's disease on chromosome 16.

Crohn's disease (CD) and ulcerative colitis are the major forms of chronic inflammatory bowel diseases in the western world, and occur in young adults with an estimated prevalence of more than one per thousand inhabitants. The causes of inflammatory bowel diseases remain unknown, but genetic epidemiology studies suggest that inherited factors may contribute in part to variation in individual susceptibility to Crohn's disease. A genome-wide search performed on two consecutive and independent panels of families with multiple affected members, using a non-parametric two-point sibling-pair linkage method, identified a putative CD-susceptibility locus on chromosome 16 (P less than 0.01 for each panel). The localization was centered around loci D16S409 and D16S419 by using multipoint sibpair analysis (P less than 1.5x10(-5)). This region of the genome contains candidate genes which may be relevant to the pathogenic mechanism of inflammatory bowel diseases.

Alleles↗
PubMed1996

Are HLA-DR or TAP genes genetic markers of severity in ulcerative colitis?

The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n = 91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n = 200) were included. HLA-DRB1*03 was less frequent in UC patients than in healthy controls (8% vs 28%, PC < 0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively, (PC < 0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Intravenous cyclosporine in attacks of ulcerative colitis: short-term and long-term responses.

The present study reports the results of intravenous cyclosporine in 32 patients with refractory and/or severe attacks of ulcerative colitis (UC). Twenty of 32 patients responded to intravenous cyclosporine; cyclosporine was clinically effective and improved colonic lesions. However, one colonic perforation and one postoperative death were observed in two patients with severe endoscopic colitis who had failed to reach clinical remission with high-dose corticosteroids and cyclosporine. Moreover, after a median follow-up of 190 days, only one-third of the patients avoided colectomy. No predictive factor of response to cyclosporine was identified. This study confirms that cyclosporine is effective in severe UC but suggests that its use could be associated with serious complications in patients with severe lesions who had failed to settle with corticosteroids and cyclosporine.

Adolescent↗
PubMed1996

Treatment of severe Crohn's disease with anti-CD4 monoclonal antibody.

BACKGROUND: Monoclonal CD4 antibodies have been proposed as a new immunosuppressant drug in the treatment of inflammatory bowel disease. We report our experience of treatment with a monoclonal anti-CD4 (B-F5) antibody in severe refractory Crohn's disease. METHODS: Twelve patients with severe refractory Crohn's disease were treated in an open clinical trial. B-F5 was given intravenously at a dose of 0.5 mg. day/kg for 7 consecutive days (patients 1-8). For patients 9-12, B-F5 was given at a dose of 0.5 mg. day/kg on the first day (day 0) and of 1 mg.day/kg on days 1-6. Follow-up examinations were carried out at days 8, 15, 22 and 30. Endoscopic evaluation was performed on days 0 and 30 in eight of 12 patients. RESULTS: Immediately after the first infusion, one patient had dyspnoea and tachycardia requiring cessation of the treatment. Among the 11 patients who received the complete course of treatment, two had prolonged clinical improvement and two had partial clinical improvement. Significant endoscopic improvement was observed in only one patient. No sustained depletion of CD4+ cells could be observed. CONCLUSION: In this uncontrolled open trial, monoclonal anti-CD4 B-F5 antibody was not successful in severe Crohn's disease.

Adolescent↗
PubMed1996

Effect of intrajejunal elemental diet perfusion on local secretion of soluble CD4 and CD8.

The effects of nutrients on the mucosal immune system are poorly understood. The aim of this work was to study the cellular mucosal immune response to intrajejunal perfusion of an elemental diet (ED) or a control (C) electrolyte solution by measuring jejunal secretion of soluble CD4 (sCD4) and sCD8. sCD4 and sCD8 are markers of helper/inducer and suppressor/cytotoxic regulatory functions of T cells, respectively. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with C for 80 min and then with ED containing 21.3 g/l of free amino acids and 104.2 g/l of oligosaccharides for 100 min. Jejunal fluid and serum concentrations of sCD4 and sCD8 were measured and their jejunal outputs calculated. When compared with C perfusion, jejunal perfusion with the ED resulted in a significant increase of sCD8 but not sCD4 jejunal secretion rates. sCD8 jejunal values increased early after ED perfusion and stayed at roughly the same level during the perfusion. Serum concentrations of sCD4 and sCD8 were not modified during ED perfusion. These data support the hypothesis that ED suppresses the immunologic tone of the gut, which could explain its beneficial effect in the management of intestinal inflammatory disease.

Adult↗
PubMed1996

Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenoma.

BACKGROUND & AIMS: Rectosigmoid villous adenomas (RVAs) account for approximately 10% of all colorectal tumors. They have distinct pathological features, including abundant mucus secretion, possible malignant transformation, and multiple recurrences after conservative treatment. The aim of this study was to determine the nature of any changes in mucin gene expression in RVAs. METHODS: In situ hybridization was used to examine mucin messenger RNA expression in a series of 22 patients with an RVA. Five normal rectal and colonic mucosae and five rectal adenocarcinomas were used as controls. RESULTS: In the 22 RVAs, we found an overexpression of MUC2 and an aberrant expression of MUC5AC. This MUC5AC expression was more intense in RVAs with low-grade dysplasia than in those cases with high-grade dysplasia. Moreover, in 4 cases, it was detected at a distance from the tumor in areas previously considered as normal by endoscopic and histological examination. CONCLUSIONS: MUC5AC seems to be a specific marker for RVAs and thus may be useful for the early detection of RVA recurrences after endoscopic laser treatment.

Adenoma, Villous↗
PubMed1996

Mesalamine in Crohn's disease with steroid-induced remission: effect on steroid withdrawal and remission maintenance, Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives.

BACKGROUND & AIMS: Steroid dependence and early relapse are frequent after a prednisolone-induces remission in Crohn's disease. The aim of this trial was to test whether mesalamine started at the onset of steroid tapering increases the rate of weaning from prednisolone and reduces the relapse rate after prednisolone cessation. METHODS: One hundred fifty patients with active Crohn's disease were administered oral prednisolone (1 mg.kg(-1). day(-1)) x 3-7 weeks; 129 patients went into clinical remission and were randomized to Pentasa (4 g . day(-1)) or placebo, administered until weaning and for 1 year thereafter. RESULTS: Groups were similar for clinical and biological items collected initially. Weaning failure rate was 30% and 12% in the placebo and mesalamine arms, respectively. At the end of the trial, 9 of 36 patients administered placebo and 14 of 48 administered mesalamine were in remission. Both groups had similar time to relapse curves in the postweaning year; after adjusting for risk factors (high Crohn's Disease Activity Index, white blood cell count of >9 x 10(9) /l-1 at weaning, and use of a medical treatment in the month before inclusion), Pentasa was found to be superior to placebo. CONCLUSIONS: After a prednisolone-induces remission in Crohn's disease, mesalamine facilitates steroid withdrawal and, during the postweaning year, may reduce the relapse rate in certain patient subgroups.

Adolescent↗
PubMed1996

Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis.

BACKGROUND & AIMS: Eosinophilic gastroenteritis (EG) is characterized by an eosinophilic infiltration of the gastrointestinal tract. The mechanism for the intestinal recruitment of eosinophils in EG remains unknown. Eosinophil recruitment and activation is induced by three main cytokines: interleukin (IL) 3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5. The aim of this study was to examine the immunoreactivity for IL-3, GM-CSF, and IL-5 within the duodenal and colonic mucosa of 10 patients with EG. METHODS: Endoscopic biopsy specimens were obtained from 10 patients with EG and 10 controls. IL-3, GM-CSF, and IL-5 was evaluated by immunohistochemistry. Electron microscopy combined with immunogold staining was used to identify the labeled cells and to localize these growth factors ultrastructurally. RESULTS: A significant increase in the number of eosinophils was found in both duodenal and colonic mucosa from all 10 patients with EG compared with controls. In the same tissue, immunohistochemistry detected IL-3, GM-CSF, and IL-5 in 9 of 10 patients with EG. The one exception had received treatment with steroids. These cytokines were not detected in the control group. Ultrastructurally, IL-3, GM-CSF, and IL-5 were localized in the granule matrix of eosinophils. CONCLUSIONS: The release of these cytokines with autocrine and/or paracrine activities by eosinophils may be involved in the persistence of intestinal eosinophil infiltration.

Adolescent↗
PubMed1996

Clinical characteristics of Crohn's disease in 72 families.

BACKGROUND & AIMS: Familial aggregation argues for genetic susceptibility to Crohn's disease. The aim of this study was to compare the age of onset and the clinical features of Crohn's disease between patients with familial disease and those with sporadic disease and investigate the concordance for disease location and type among relatives with Crohn's disease. METHODS: Seventy-two families with 2 (n = 55), 3 (n = 8), 4 (n = 6), and 5 or more (n = 3) affected first-degree relatives were selected for the study. A population of 1377 patients with sporadic nonfamilial Crohn's disease was used for comparison. RESULTS: Clinical data were obtained from 176 patients with familial Crohn's disease (79 men and 97 women). Median age at onset was younger in familial Crohn's disease than in sporadic cases: 22 vs. 26.5 years (P < 0.01). In familial cases, fewer patients had exclusively colonic involvement and more patients had both small bowel and colonic involvement. Among relatives of families with 2 affected members, 56% were concordant for disease location and 49% for disease type. These percentages reached 83% and 76%, respectively, within families with more than 2 affected members. CONCLUSIONS: Patients with familial Crohn's disease are characterized by an early age at onset with more extensive disease and may represent a homogeneous clinical subgroup with a particularly strong genetic influence.

Adolescent↗
PubMed1996

Chronic pancreatitis: a complication of sarcoidosis?

Gastrointestinal localizations of sarcoidosis are rare. A total of 14 cases of pancreatic involvement in sarcoidosis has been reported previously. We report here a case of late onset idiopathic chronic pancreatitis diagnosed at the same time as sarcoidosis with liver, colonic, renal, mediastinal and neurologic involvement in a 56-year-old man. This case further suggests a possible relationship between idiopathic chronic pancreatitis and multisystem diseases.

Age of Onset↗
PubMed1996

Methotrexate for the treatment of refractory Crohn's disease.

BACKGROUND: Previous studies suggested that methotrexate has beneficial effects in patients with Crohn's disease. We report our experience with this agent in patients with chronic active Crohn's disease who previously failed to improve with conventional treatment, including azathioprine in most cases. METHODS: Between June 1988 and June 1992, 39 patients with refractory Crohn's disease were treated with methotrexate. In patients with active disease, clinical remission was defined by a Harvey-Bradshaw index of less than 4. For patients also taking corticosteroids, the dates of remission and complete steroid withdrawal were recorded. For patients who achieved clinical remission, and those in clinical remission when methotrexate was started, the relapse rate on methotrexate therapy was noted. RESULTS: In the 37 patients with active disease at methotrexate initiation, the probability of remission was 72% at 3 months. The probability of remission and steroid withdrawal was 42% at 12 months. In patients on clinical remission, the probability of relapse on methotrexate was 58% at 12 months. Twenty-two patients experienced side-effects, but these only warranted methotrexate discontinuation in four cases. CONCLUSIONS: Methotrexate appears effective in most patients with refractory Crohn's disease and its short-term toxicity is acceptable, but the long-term benefit seems more limited.

Adolescent↗